Titelbaum Moran, Brant Boris, Baumel Daniel, Burstein-Willensky Alina, Perez Shira, Barsheshet Yiftah, Avni Orly
Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
iScience. 2021 Sep 9;24(10):103093. doi: 10.1016/j.isci.2021.103093. eCollection 2021 Oct 22.
Following their first interaction with the antigen, quiescent naive T-helper (Th; CD4) cells enlarge, differentiate, and proliferate; these processes are accompanied by substantial epigenetic alterations. We showed previously that the epigenetic regulators the polycomb-group (PcG) proteins have a dual function as both positive and negative transcriptional regulators; however, the underlying mechanisms remain poorly understood. Here, we demonstrate that during Th cell differentiation the methyltransferase activity of the PcG protein Ezh2 regulates post-transcriptionally inducible assembly of intranuclear actin filaments. These filaments are colocalized with the actin regulators Vav1 and WASp, vertically oriented to the T cell receptor, and intermingle with the chromatin fibers. Ezh2 and Vav1 are observed together at chromatin-actin intersections. Furthermore, the inducible assembly of nuclear actin filaments is required for chromatin spreading and nuclear growth. Altogether these findings delineate a model in which the epigenetic machinery orchestrates the dynamic mechanical force of the intranuclear cytoskeleton to reorganize chromatin during differentiation.
在与抗原首次相互作用后，静止的初始辅助性T细胞（Th；CD4）会增大、分化并增殖；这些过程伴随着大量表观遗传改变。我们之前表明，表观遗传调节因子多梳蛋白组（PcG）蛋白作为正性和负性转录调节因子具有双重功能；然而，其潜在机制仍知之甚少。在这里，我们证明在Th细胞分化过程中，PcG蛋白Ezh2的甲基转移酶活性在转录后调节核内肌动蛋白丝的诱导组装。这些丝与肌动蛋白调节因子Vav1和WASp共定位，垂直于T细胞受体定向，并与染色质纤维交织。在染色质 - 肌动蛋白交叉点共同观察到Ezh2和Vav1。此外，核肌动蛋白丝的诱导组装是染色质扩展和核生长所必需的。总之，这些发现描绘了一个模型，其中表观遗传机制在分化过程中协调核内细胞骨架的动态机械力以重组染色质。
